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Page 146 Shad. J Transl Genet Genom 2023;7:141-65 https://dx.doi.org/10.20517/jtgg.2023.11

Table 2. Genetic predictors of clozapine response

Treatment Assessment
Reference Genetic variant Sample size Ethnicity Clozapine dose Significance
duration measure
Pharmacokinetic Genetic Markers - CYP P450 Enzymes
Eap et al., CYP1A2*1F 33 (4/29) Four smoking Dose range 450-800 NA CGI 2 patients with marked and 2 with moderate
[54]
2004 schizophrenia patients mg/day improvement on CGI after increasing clozapine to
were nonresponders to 1,400 mg/day
clozapine
Balibey et al., CYP1A2*1F 97 Turkish Mean dose: 308 ± 92 18 weeks BPRS 2.4-fold higher lack of response in patients with
[55]
2011 mg/day homozygosity for CYP1A2*1F (P = 0.02)
De Brito et al., CYP1A2*1F Clozapine Brazilian Mean dose in CLZ non- 2 years BPRS 74% CLZ nonresponders homozygous vs. 33%
[56]
2015 responders = 54; responders = 593 ± 114 CLZ responders homozygous for CYP1A2*1F
Clozapine non- mg/day (P = 0.0002)
responders = 27 Mean dose in CLZ
responders: 535 ± 116
mg/day
Piatkov et al., CYP2C19*17 rs12248560 45 Australian (Caucasian, NA 3 and 12 months Not assessed Homozygosity for CYP2C19*17 was associated
[57]
2017 Asian, Pacific Islander) formally with a lower CLZ/NCLZ ratio and improved
clinical response (P = 0.049)
Lee et al., ABCB1 rs7787082, 15 Korean Mean dose: 319.0 ± 133.1 > 6 months CGI-I 19/20 patients were responders with A/A for
[58]
2012 rs10248420 mg/day ABCB1 rs7787082 (corrected P = 035) vs. 20/31
responders with A/A for ABCB1 rs10248420
(corrected P = 0.046)
Dopamine-Associated Genes
Shaikh et al., DRD3 Ser9Gly 133 Caucasians NA BPRS 53% non-responders vs. 36% responders with
[59]
1996 DRD3 Ser9Gly 1-1 genotype (P = 0.04)
Scharfetter et al., DRD3 Ser9Gly 32 Pakistani Maximum dose = 600 6 months BPRS Better clozapine response in patients with Gly-9
[60]
1999 mg/day allele than Ser-9 allele (P = 0058)
Hwang et al., DRD3 rs2134655 in 232 Caucasians and African NA At least 6 BPRS, BPOS, BNEG -A allele (allele 1) of rs2134655 associated with a
[61]
2010 Caucasian samples, Americans months better response on the BPOS (P = 0.007) in
rs1394016 in African Caucasians.
American samples -A dose-dependent relationship between the T
allele of rs1394016 and better response on the
BNEG scale (P = 0.018) in African Americans

Huang et al., DRD2 rs2514218 208 Caucasian and African NA 6 months BPRS DRD2 rs2514218 significant association b/w G/G
[62]
2016 American genotype and BPRS change (adjusted P = 0.033)
Hwang et al., DRD2, Taq1B, rs1125394, 232 Caucasian and African NA At least 6 BPRS, BPOS -African Americans with the TaqIB B1 allele were
[63]
2006 and rs2242593 American months associated with a lesser response than those
without (P =0.025)
-African Americans with allele 1 of rs1125394
with improved response
(P = 0.001)
-1-1 genotype of rs2242593 with a better